Current approaches to treating disease with therapeutic proteins include both administration of proteins produced in vitro and gene therapy. In vitro production of a protein generally involves the introduction of exogenous DNA coding for the protein of interest into appropriate host cells in culture. Gene therapy methods, on the other hand, involve administering to a patient genetically engineered cells, plasmids, viruses that contain a sequence encoding the therapeutic protein of interest.
Certain therapeutic proteins may also be produced by altering the expression of their endogenous genes in a desired manner with gene targeting techniques. See, e.g., U.S. Pat. Nos. 5,641,670, 5,733,761, and 5,272,071, WO 91/06666, WO 91/06667, and WO 90/11354, all of which are incorporated by reference in their entirety.